Humoral Immunity Flashcards
(140 cards)
1
Q
what is clonal expansion
A
once BCR binds to antigen and it starts to proliferate (go through mitosis)
2
Q
once BCR binds antigen it will secrete
A
low levels of IgM
3
Q
what is the significance of IgM being secreted
A
signifies early phase of humoral immune response
4
Q
what are the costmulators that will be expressed after BCR binds antigen
A
B7 costimulators
increased expression of cytokine receptors
5
Q
where do cytokine receptors migrate to
A
T cells
6
Q
increased expression of costimulators and cytokine receptors lead to
A
reactivation of t cell
7
Q
a t cell will do nothing unless
A
recognizing antigen present by MHC
8
Q
TI-1 antigen tend to induce
A
polyclonal b cell activation
they activate b cell regardless of specificity of b cell receptor
9
Q
ex of TI-1 antigen
A
LPS
10
Q
do TI-2 antigens induce polyclonal b cell activation
A
no
11
Q
TI-2 antigens require
A
repeating epitopes
12
Q
ex of TI-2 antigen
A
pneumonal polysaccharide
13
Q
TD antigen require
A
t cell help for optimal production of antibody
14
Q
important feature of TD antigen
A
can generate antigen specific responses (in infants?)
15
Q
kids under two, their bodies have really hard time recognizeing
A
TI-2 antigen
16
Q
how are vaccines given to children for pneumococcal polysaccharide (pnemonia)
A
its TI-2 antigen so their body is bad at recognizing it, have to trick their body into having a response. have to link the TI-2 antigen and basically convert it to TD antigen b/c link it to polypeptide
17
Q
there is no antibody response to what in kids under 2
A
pure polysaccharide
18
Q
TD antigen response require help from
A
CD4 T cells
19
Q
TD antibody response, after it finds antibody it will give rise to
A
plasma cells & memory B cells
20
Q
affinity of antibody secreted after help from T cell is much higher than
A
affinity of antigen secreted earlier in T cell indepdent phase
21
Q
once b and t cell are activated what will happen
A
they will migrate towards each other
22
Q
b and t cells migrate toward each other, what happens next
A
t cell help for TD antigens
23
Q
after first t cell b cell interaction the b cell is going to
A
start to mutate the rearrange vj and vdj chain and generate antibody of higher affinity than the original antibody that was secreted against the antigen
24
Q
the second t cell and be cell interaction will result in
A
isotype switching
now b cell will not make IgM, it will make isotype more appropriate for the pathogen we are dealing with
25
infection in respiratory what Ig would b cell make
IgA
26
if infection in tissue what Ig would b cell make
IgG
27
after second b cell t cell interaction what cells will be made
plasma cells
| memory b cells
28
for TD resonse need to activate
CD4 T cell (helper)
29
where does activation of CD4 happen
paracortex of lymph node
30
activation of CD4 mediated by
dendritic cell
31
activated CD4 T will do what
provide help to B cell once activated through its BCR
32
for B cell to receive signals it has to
reactivate CD4T cell (so it is functioning as APC)
33
where does first B cell T cell interaction take place
edge of paracortex
34
once b cell binds CD4 what does it do
migrate to follicle and start to mutate the rearranged VJ and VDJ of its BCR (antibody response is maturing)
35
affinity maturation of Ig response is what
when B cell rearranges its VD and VDJ chains after interacting with CD4
36
after BCR is mutated to have higher affinity, what happens
second B cell T cell interaction
37
where does second B cell T cell interaction take place
in the follicle
38
a single dendritic cell can present antigen to
multiple T cells at one time
39
FDC stands for
follicular dendritic cell
40
don't confuse FDC with
dendritic cell! they are very different
41
when B cells are traveling down and they encoutner FDC what do they do
scan it to see if it has antigen that the B cell can use
42
b cells become activated on surface of
FDC in B cell area
43
T cells become activated by
dendritic cells in paracotex of lymph node or in T cel area in genearl
44
once T cells activated, they migrate
towards B cells, and B cells toward T cells
45
when the T and B cells meet B cell acts as
APC
46
signal 1 of B cell T cell interaction is delivered through
BCR and co-receptors
47
signal 2 of B cell T cell interaction is delivered through
CD40L (ligand)
48
where is CD40L found
surface of T cell
49
CD40L is only expressed
briefly on T cell following it's activation
50
why does B cell need to reactivate T cell
so that CD40L will be re-expressed on it's surface
51
where is CD40 located
on B cell
52
when CD40 and CD40L bind what happens
stimualtes T cell to secrete cytokines towards B cell, they will dictate what will happen in next stage of antibody response
53
CD40 CD40L interaction crucial fo
generation of antibody
| isotype switching
54
B cell is stimulated to proliferate in response to
cytokine secreted by T cell
55
what is one of the most important cytokines secreted by helper t cell
interleukin 4
56
interleukin 4 is
main cytokine that promotes B cell proliferation
57
what is main cytokine that promotes B cell proliferation
interleukin 4
58
after the second interaction with t cell what does b cell do
returns to follicle, follicle becomes secondary follicle, enlarges, intense proliferation, ultimately will give rise to germinal center
59
germinal center is site of
intense b cell proliferation and death of b cells
60
Tfh stands for
follicular helper t cell
61
what doe Tfh do
helps the b cells that survive the intense proliferation to undergo isotype switching
62
following activation of b cells in secondary lymphoid tissue, produce on surface of B cell the BCR and will start to secret
immunoglobulin
63
initial immunoglobulin secreted
IgM
64
T dependent response is characterized by
increase in affinity of antibody that is produced over the course of the response
65
affinity maturation is result of
mutation
66
mutation is focused on
rearranged VJ and VDJs
67
rate of mutation occurs at
much higher rate of mutation than normal mutation,
68
process of mutation is called
somatic hypermutation or SHM
69
SHM stands for
somatic hypermutation
70
SMH is
molecular mechanism that gives rise to affinity maturation of antibody response
71
after b cells that are now secreting high affinity Ig have been selected they will receive help
again from T cells - now isotype switching
72
isotype switching
B cells switchin from producing IgM to another isotype
73
following receipt of T cell help the ratio of amoutn of antibody by B cell to BCR
increase (secreting a lot mroe antibody!)
74
b cells that have mutated their VJ and VDJ so they produce higher affinity antibody will now
interact again with T cells - follicular helper T cells - cause isotype switching
75
after isotype switching, what happens
differentiate into memory and plasma cells
76
what kinds of mutations introduced in SHM
point mutations
77
effect of point mutations during SHM
unknown - they could have no affect on affinity, decrease affinity, or have incrreased affinity of antibody produced
78
after SHM have to
select for the b cells that have mutated their variable regions so they bind to antigen with higher affinity
79
what enzyme is needed to induce the point mutations during SHM
AID - activation-induced cytidine deaminase
80
what does AID stand for
activation induced cytidine deaminase
81
what happens to b cells that have not increased the affinity of their surface Ig
DEATH
| the hunger games
82
the mutated b cells that contact the antigen get
survival signal
83
what does AID do
deaminates cytidine resiudes in DNA
so makes C to U
the mismatch is then repaired
84
during isotype switching what happens to light chain
it is unaffected
| the variable region doesn't change
85
why is IgM always the first one produced
just b/c it lie nearest to the VDJ
86
isotype switching is dependent on
T cell
| microenviornment
87
describe what happens during isotype switching
transcription of H chain constant region genes and loss of intervening DN. variable region is not altered!
88
AID induces nicks in DNA where
switch regions
89
where are switch regions located
upstream of the constant region (except Cdelta)
90
the DNA that lies b/w the constant DNA and the segment we are switching to, what happens to it?
it gets looped out and is excised from the chrom. DNA is permanently modified
91
class switch recombination only happens in what cell
B cell
92
is the reading frame ever affected in isotype switching?
no
93
describe the secretion of cytokine from T cell
it is directional. it is pointed at the B cell at the point of contact
94
where does SMH occur
in centroblasts in dark zone of germinal center
95
what is a centroblast
activated b cell that is large and proliferating in the germinal center
96
once mutation has finished and b cell express the mutated b cell receptor the cell is now called
centrocyte
97
centrocyte have to compete to do what
to bind to antigen on dendritic cells, the ones that mutated and have high affinity outcompete and live!
98
the surviving b cell (after competition) will express what
bcl - it is anti-apoptotic
99
the isotype the b cell will switch to is dictated by what
the cytokines made by the t cell
100
TGFbeta promotes
class switching to IgA
101
cytokines secreted by T cells dictate whether B cell differentiate into
memory or plasma cells
102
What does IL-10 do in regards to t cell and b cell
promotes differentiation of b cell into plasma cell
103
What does IL-4 do in regards to t cell and b cell
promotes differentiation of b cell into memory cell
104
disease that does not allow b cell to switch from IgM to another isotype
X-linked Hyper IgM syndrome
105
mutation in CD40L will have what disease
X-linked Hyper IgM syndrome
106
X-linked Hyper IgM syndrome
| describe
normal number of t and b cells
only IgM, no class switching
mutated CD40L
no germinal centers
107
following exposure to pathogen, we will get initial burst of
IgM followed by class switching
108
level of antibody generated during primary response is maximal when
10-12 days following exposure to antigen
109
antibody level 10-12 days and after, hwat will level be after
the level of antibody will persist
110
what is the functin of having the antibody level stay high after infection is gone
protection
111
memory cells will provide protection against
rexposure
112
where do plasma cells go
migrate to variety of site and secrete antibody into plasma
| most important might be bone marrow
113
plasma cells that migrate to bone marrow
account for 1/2 of circulating Ig
114
about 1/2 of Ig in plasma resluts from Ig secretion by plasma cells that have
migrated to bone marrow
115
t cell are activated in
paracortex
116
b cells are activated in
follicles
117
once t cell is activated what happens to the population
expands - make a lot more fo them that are specific for the antigen
118
effector t and b cells by far
outnumber the memory t and b cells
119
in individuals prior to exposure of antigen, the frequency of antigen specific b cells that are capable of reacting agains the antigen are
low
120
whichever you clss switch to will be decided by
cytokines
121
affinity of antibody produced in primary response
low
122
affinity of antibody toward end of primary response
increases
123
in secondary response, much higher frequency of
antigen reactive cells
124
isotype of antibody produced during secondary response is generally
```
IgA, G, or E (class switched)
but some IgM can be produced
```
125
as a result of the somatic hypermutation that occurs towards the end of the primary response, the affinity of antibody secreted during secondary response
is much much higher than affinity produced during primary response
126
why is affinity so much higher during secondary response
somatic hypermutation
127
why is secondary response dominated by IgG, A, E?
during secondary response the naive b cells that are capable of reacting against the antigen, their activation is inhibited b/c naive b cells express negative coreceptor
128
memory b cells do not have
negative co-receptor
129
within a week or so of infection will get detectible levels of
low affinity IgM
130
somatic mutation doesn't just happen once,
it keeps happening, a constant thing of somatic hypermutation and selection, so b cells are cycling b/w light and dark zone
131
where is somatic hypermutation happenign
dark zone
132
the migration of t cells and b cells during t dependent response is controlled by
chemokines binding to chemokine receptors
133
in response to cytokines produced by t cells
b cells will proliferate
134
ultimately what will happen to germinal center
it will be broken up so the follicle can be used again
135
isotype switching is dependent on what enzyme
AID
136
when re-expose to antigen, within a few days
have levels of high affinity antibody, equivalent to levels at peak of primary response, then secrete even higher levels of antibody
137
during late primary response get production of
IgG
138
what is dominant isotype during most secondary response
IgG
139
because IgM is hallmark of primary response, production of IgM usually indicates you have
active infection
140
IgG detection usuallly indictates
it doesn't necesarilly mean there's an active infection. it can be maintained for many months following infection
